Abstract
SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and medial prefrontal cortex, increasing the vulnerability to stress related disorders. This is supported by observing the beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in both posttraumatic stress disorder and SARS-CoV-2 critical illness. In this narrative review, we take a closer look at the virus-host dialog and its impact on the renin-angiotensin system, mitochondrial fitness, and brain-derived neurotrophic factor. We discuss the role of furin cleaving site, the fibrinolytic system, and Sigma-1 receptor in the pathogenesis of psychological trauma. In other words, learning from the virus, clarify the molecular underpinnings of stress related disorders, and design better therapies for these conditions. In this context, we emphasize new potential treatments, including furin and bromodomains inhibitors.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of COVID-19, spread rapidly throughout the world and was declared a pandemic in March 2020 (Wu and McGoogan, 2020)
The fibrinolytic system regulates thrombolysis and neuroplasticity (Wang X.L. et al, 2016). Both severe COVID-19 and posttraumatic stress disorder (PTSD) were associated with upregulated plasminogen activator inhibitor 1 (PAI-1), a negative type plasminogen activator (tPA) regulator, indicating that targeting this protein may be therapeutic for both diseases (Cesari et al, 2010; Idell et al, 2017; Bouarab et al, 2021)
Recent bioinformatic studies established that some SARSCoV-2 antigens mimic human proteins expressed by neurons, astrocytes, and cerebral endothelial cells (CECs), predisposing to PTSD
Summary
Follow this and additional works at: https://scholarworks.utrgv.edu/som_pub Part of the Neurosciences Commons. Recommended Citation Zapata-Martín del Campo CM, Maldonado JC, Jafri N, Cummings MA, Maurer S and Kozlakidis Z (2021) PTSD as an Endothelial Disease: Insights From COVID-19. Authors Adonis Sfera, Carolina Osorio, Leah Rahman, Carlos M. Zapata Martín del Campo, Jose Campo Maldonado, Nyla Jafri, Michael Cummings, Steve Maurer, and Zisis Kozlakidis. This article is available at ScholarWorks @ UTRGV: https://scholarworks.utrgv.edu/som_pub/455. Adonis Sfera1,2*, Carolina Osorio, Leah Rahman, Carlos Manuel Zapata-Martín del Campo, Jose Campo Maldonado, Nyla Jafri, Michael Allen Cummings, Steve Maurer and Zisis Kozlakidis. Reviewed by: Hale Yapici Eser, Koç University, Turkey Isabella Zanella, University of Brescia, Italy. Specialty section: This article was submitted to Cellular Neuropathology, a section of the journal
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